The long-term objective of the proposed work is to define the major features of the life cycle of pathogens transmitted by the deer tick Ixodes dammini, with reference to identifying conditions that affect infection of the vector tick as well as development of parasites infectious for the reservoir. In particular, we shall (1) determine the route by which kinetes of Babesia microti migrate from the gut of the vector to the salivary glands and describe the development of the kinete; (2) determine whether sporozoites of B. microti may invade lymphoid cells or other non-erythrocytic cells and whether such infected cells may stably transform; (3) compare larva-to-nymph and nymph-to-adult transstadial transmission of B. microti infection in the vector, and resolve the paradox presented by our observation of kinetes in the hemolymph of adult ticks (Can infection be inherited?); (4) develop a technique for feeding hard ticks from a capillary tube; (5) identify the stimulus for gamete formation; (6) identify the stimuli that regulate maturation of sporozoites of I. dammini; (7) describe the development of the Lyme spirochete in I. dammini and evaluate the components of vector competence of I. dammini for this pathogen (including the possibility of inherited infection); (8) describe the pharmacology of tick-bite with particular reference to the possibility that tick-secreted prostaglandin E2 may prepare the skin for infection by the Lyme spirochete or sporozoites of B. microti; (9) describe the time-course of events in feeding and salivation by I. dammini with particular reference to regurgitation and the rate of salivation; (10) compare vector competence of B. microti in I muris and other potential vector ticks. This project applies experimental and electron microscopic techniques to describe and explain morphogenesis of two new agents of public health importance.